title: Levels of anti-double-strained DNA but not antinuclear antibodies are associated with treatment efficacy and adverse outcomes in Crohn's disease patients treated with anti-TNFα.
abstract: OBJECTIVE
  Treatment of Crohn's disease (CD) by infliximab (IFX) has been associated with the induction of antinuclear (ANA) and anti-double strand DNA (dsDNA) autoantibodies and in some studies the formation of dsDNA antibodies was associated with lupus-like syndromes. The aims of this study were to analyse the relationship between the development of ANA and dsDNA antibodies during anti-tumor necrosis factor (TNF)α therapy and the clinical efficacy or adverse outcome in patients with inflammatory bowel disease (IBD).
  
  
  METHODS
  Data of 96 CD patients (age at presentation: 25.1 years, folow-up: 5 years, males/females 43/53) treated with anti-TNFα for at least one-year were analyzed. Records of a total of 198 one-year treatment cycles were collected and levels of autoantibodies were determined at induction and after one-year treatment periods.
  
  
  RESULTS
  The majority of CD patients had ileocolonic (67.4%) and complicated disease (B2-B3: 72.6%) with perianal lesions (63.2%). At any time ANA or dsDNA positivity was 28.6% and 18%. Elevated level of ANA at induction or during anti-TNFα therapy was not associated with treatment efficacy or development of adverse outcomes. In contrast, treatment efficacy (dsDNA positivity no/partial response vs. remission: 68.5% vs. 31.5%, P=0.003) was inferior and adverse outcomes were more frequent in patients with dsDNA positivity during the anti-TNFα therapy in both univariate analysis and in logistic regression models (OR efficacy: 4.91, 95%CI: 1.15-20.8; OR adverse outcome: 3.81,95%CI 1.04-13.9).
  
  
  CONCLUSIONS
  Our data suggest that development of dsDNA during biological therapy may be associated with suboptimal treatment efficacy and adverse outcomes in CD patients.
authors.affiliation: 1st Department of Medicine, Semmelweis University, Budapest, Hungary.
authors.forename: Lajos S S
authors.initials: LS
authors.lastname: Kiss
authors.forename: Barbara D
authors.initials: BD
authors.lastname: Lovasz
authors.forename: Petra A
authors.initials: PA
authors.lastname: Golovics
authors.forename: Zsuzsanna
authors.initials: Z
authors.lastname: Vegh
authors.forename: Klaudia
authors.initials: K
authors.lastname: Farkas
authors.forename: Tamas
authors.initials: T
authors.lastname: Molnar
authors.forename: Karoly
authors.initials: K
authors.lastname: Palatka
authors.forename: Maria
authors.initials: M
authors.lastname: Papp
authors.forename: Anna
authors.initials: A
authors.lastname: Mohas
authors.forename: Blanka K
authors.initials: BK
authors.lastname: Szilagyi
authors.forename: Szandra A
authors.initials: SA
authors.lastname: Fekete
authors.forename: Michael
authors.initials: M
authors.lastname: Mandel
authors.forename: Peter L
authors.initials: PL
authors.lastname: Lakatos
mesh_terms: D000328:Adult; D000974:Antibodies, Antinuclear / Q000097:blood*; D000911:Antibodies, Monoclonal / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D003424:Crohn Disease / Q000097:blood / Q000175:diagnosis / Q000188:drug therapy* / Q000276:immunology; D004247:DNA / Q000276:immunology*; D005260:Female; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D000069285:Infliximab; D016015:Logistic Models; D008297:Male; D015999:Multivariate Analysis; D016017:Odds Ratio; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome; D014409:Tumor Necrosis Factor-alpha / Q000037:antagonists & inhibitors* / Q000378:metabolism; D055815:Young Adult
chemical_list: D000974:Antibodies, Antinuclear; D000911:Antibodies, Monoclonal; D015415:Biomarkers; D007166:Immunosuppressive Agents; D014409:Tumor Necrosis Factor-alpha; D004247:DNA; D000069285:Infliximab